Long-term outcomes following intravascular lithotripsy (IVL) for calcified coronary lesions: A Real-World Multicenter European Study.

OBJECTIVES: To explore the long-term clinical outcomes following intravascular lithotripsy (IVL) in calcified coronary lesions from a real-world population. BACKGROUND: IVL is a relatively new but promising modality for treating coronary calcified lesions, but there is a dearth of long-term outcome data from real-world patients. METHODS: This was a multicenter, observational study in which we enrolled all patients treated with IVL from November 2018 to February 2021 from eight centers in Europe and the United Kingdom. Procedural success, complications, and clinical outcomes (cardiac death, target vessel myocardial infarction [TVMI], target lesion revascularization [TLR], and MACE [major adverse cardiac events, the composite of cardiac death, TVMI, and TLR]) were assessed. RESULTS: In total, 273 patients with a mean age of 72 ± 9.1 years were treated with IVL. Major comorbidities included diabetes mellitus (n = 110, 40%) and chronic kidney disease (n = 45, 16%). Acute coronary syndrome accounted for 48% (n = 132) of patients, while 52% (n = 141) had stable angina. De novo lesions and in-stent restenosis accounted for 79% and 21% of cases, respectively. Intravascular imaging was used in 33% (n = 90) of patients. An upfront IVL strategy was adopted in 34% (n = 92), while the rest were bailout procedures. Adjuvant rotational atherectomy ("RotaTripsy") was required in 11% (n = 31) of cases. The procedural success was 99%. During a median follow-up of 687 days (interquartile range: 549-787), cardiac death occurred in 5% (n = 14), TVMI in 3% (n = 8), TLR in 6% (n = 16), and MACE rate was 11% (n = 30). CONCLUSION: This is the largest multicenter registry with a long-term follow-up showing the remarkably high procedural success of IVL use in calcified coronary lesions with low rates of hard endpoints and MACE.

Safety and efficacy of interrupting dual antiplatelet therapy one month following percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

Very short duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has recently attracted a lot of attention with the introduction of newer generations stents. This is appealing, especially in patients at high bleeding risk. However, none of the trials were powered for the individual ischemic and bleeding endpoints. All randomised controlled trials (RCTs) investigating one-month versus routine duration of DAPT in patients undergoing PCI and reporting outcomes from the time of cessation of DAPT (1 month) to 1 year were eligible for inclusion in the meta-analysis. The pooled risk ratios (RR) with their 95% confidence interval (CI) were calculated with the random-effects model using the Mantel-Haenszel method. Four RCTs involving 26,576 patients were included in this meta-analysis. Cessation of DAPT after 1 month was associated with significantly less major bleeding [RR 0.70, 95%CI (0.51-0.95), P = 0.02, heterogeneity (I2) = 42%]. There was no statistically significant difference in all-cause mortality [RR 0.84 (95%CI 0.69-1.03), P = 0.10, I2 = 0%] and stroke [RR 0.71 (95%CI 0.45-1.13), P = 0.15, I2 = 42%] when compared to routine duration of DAPT. There was also no difference in myocardial infarction (MI) [RR 1.12 (95%CI 0.91-1.39), P = 0.28, I2 = 0%], and definite or probable stent thrombosis [RR 1.49 (95%CI 0.92-2.41), P = 0.11, I2 = 0%] with cessation of DAPT after 1 month. Cessation of DAPT 1 month after PCI was associated with significantly less major bleeding, but there was no difference in the rate of all-cause mortality, stroke, MI and stent thrombosis.

Dental Caries Experience in Elementary School Students in Quebec: Surveillance Study Using ICDAS II.

OBJECTIVES: The main objective of a 2012-2013 clinical study on the oral health of Quebec elementary school students was to assess the oral health status of Grade 2 and Grade 6 students. We assessed various stages of caries and created caries indicators for primary and permanent dentitions combined. METHODS: Oral health examination of 2875 Grade 2 students and 2788 Grade 6 students, enrolled in public and private, French- and English-language schools, was carried out at schools. The examinations were performed by 16 trained and calibrated dentists using International Caries Detection and Assessment System (ICDAS) II criteria. A 3-level sampling design ensured that the study was representative for the province of Quebec. RESULTS: Mean indexes for decayed, missing, filled primary teeth (dmft) and secondary teeth (DMFT) or surfaces (dmfs and DMFS) for all stages of caries were as follows. Grade 2 students: dmft 3.96, DMFT 1.88, dmft + DMFT 5.84, dmfs 8.33, DMFS 2.96 and dmfs + DMFS 11.28. Grade 6 students: dmft 1.94, DMFT 4.98, dmft + DMFT 5.98, dmfs 4.04, DMFS 7.86 and dmfs + DMFS 9.96. Most students (90% for Grade 2 and 92% for Grade 6) had a dmfs + DMFS > 0. CONCLUSION: Tooth decay remains a public health problem in Quebec. The findings testify to the importance of reinforcing preventive measures to better control dental caries among youth. It is advantageous to use ICDAS II in the context of oral health surveillance at a population level and to present the results as a combination of primary and permanent dentitions.

Infusion of pharmaceutical-grade natural human C-reactive protein is not proinflammatory in healthy adult human volunteers.

RATIONALE: Baseline circulating concentrations of C-reactive protein (CRP) are significantly associated with cardiovascular disease risk in general populations. This modest association has been inappropriately conflated with causality, and it has been claimed that CRP is proatherogenic. Most of the known causative factors for atherosclerosis stimulate increased CRP production, but comprehensive genetic epidemiology studies provide no support for a pathogenic role of CRP. The reported proinflammatory effects of human CRP preparations on healthy cells in vitro and in healthy animals in vivo have all been produced by poorly characterized CRP preparations, demonstrably caused by impurities, or elicited by CRP made in recombinant Escherichia coli not by humans. None of the in vitro or animal findings have been reproduced with pure natural human CRP. Nevertheless, the strong proinflammatory effects of infusing recombinant bacterial CRP into humans have still been inappropriately ascribed to CRP. OBJECTIVE: To investigate the effects of infusion into healthy adult human volunteers of pure natural human CRP. METHODS AND RESULTS: Comprehensively characterized, pharmaceutical-grade, endotoxin-free, purified CRP, prepared to GMP standard from pooled normal human donor plasma was infused as an intravenous bolus in 7 healthy adult human volunteers at ≤2 mg/kg to provide circulating CRP concentrations ≤44 mg/L. No recipient showed any significant clinical, hematologic, coagulation, or biochemical changes, or any increase in proinflammatory cytokines or acute phase proteins. CONCLUSIONS: The human CRP molecule itself is not proinflammatory in healthy human adults.

Coronary Guidewires in Temporary Cardiac Pacing and Assessment of Myocardial Viability: Current Perspectives and Future Directions.

Intracoronary guidewires used in percutaneous coronary intervention can also be configured to provide temporary ventricular pacing. Trans coronary electrophysiological parameters recorded by employing coronary guidewires may have a potential role in assessing myocardial viability and could provide a means to make an immediate on-table decision about revascularisation. To date, some small studies have demonstrated the safety of this technique in temporary cardiac pacing, but further research is required to refine this approach and establish its clinical utility in myocardial viability assessment. In this review we discuss the potential role of trans coronary electrophysiology in the assessment of myocardial viability.

Transcoronary electrophysiological parameters in patients undergoing elective and acute coronary intervention.

INTRODUCTION: Percutaneous coronary intervention is performed routinely in the management of myocardial infarction with obstructive coronary disease, but intervention to arteries supplying nonviable myocardium may be harmful. It is important therefore to establish myocardial viability, and there is an unmet need in current clinical practice for real time viability assessment to aid in decision making. Transcoronary pacing to assess myocardial electrophysiological parameters may be a novel viability assessment technique which could be used in this regard. METHODS: Coronary intervention was carried out according to standard departmental procedure with standard equipment. An exchange length coronary guidewire was passed into both target and reference coronary vessels and an over-the-wire balloon or microcatheter was used to insulate the guidewire and allow electrophysiological parameters to be assessed. Readings were obtained from all major epicardial vessels and substantial branches. At each position, an intracoronary electrocardiogram was recorded, and R wave amplitude was measured. Transcoronary pacing was then performed to establish threshold and impedance for each myocardial segment. A viability cardiac MRI scan was performed for each patient. A standard segmental model was used to determine viability in each segment using an 'infarct score' based on degree of late gadolinium enhancement. Studies were reported blinded to the electrical parameters obtained from the coronary guidewire. The primary outcome was the relationship between pacing threshold and myocardial segment infarct score. Secondary outcomes included the relationship between segmental infarct score and R wave height, and between segmental infarct score and pacing impedance. Data were collected on the feasibility of studying the coronary segments as well as safety. RESULTS: Sixty-five patients presenting with stable coronary artery disease or acute coronary syndromes to Leeds General Infirmary between September 2019 and August 2021 were included in the study. Electrophysiological parameters from segments with an infarct score of zero were obtained, with wide variances seen, with no significant difference in impedance or threshold in any territory. There was a significant difference in sensitivity for segments in the right coronary artery territory for both elective and acute patients. This likely relates to reduced myocardial mass in these territories. No significant association between infarct score and sensitivity, impedance or threshold were seen. CONCLUSION: This study has established intracoronary electrophysiological parameters in both normal myocardium and areas of myocardial scar. No reliable association was seen between impedance, threshold or R wave amplitude and degree of myocardial viability, contrasting with prior findings from our group and others. More work is therefore required to fully understand the role of transcoronary pacing in this setting.

25-hydroxyvitamin D deficiency, exacerbation frequency and human rhinovirus exacerbations in chronic obstructive pulmonary disease.

BACKGROUND: 25-hydroxyvitamin D deficiency is associated with COPD and increased susceptibility to infection in the general population. METHODS: We investigated whether COPD patients deficient in 25-hydroxyvitamin D were more likely to be frequent exacerbators, had reduced outdoor activity and were more susceptible to human rhinovirus (HRV) exacerbations than those with insufficient and normal levels. We also investigated whether the frequency of FokI, BsmI and TaqIα 25-hydroxyvitamin D receptor (VDR) polymorphisms differed between frequent and infrequent exacerbators. RESULTS: There was no difference in 25-hydroxyvitamin D levels between frequent and infrequent exacerbators in the summer; medians 44.1 nmol/L (29.1 - 68.0) and 39.4 nmol/L (22.3 - 59.2) or winter; medians 24.9 nmol/L (14.3 - 43.1) and 27.1 nmol/L (19.9 - 37.6). Patients who spent less time outdoors in the 14 days prior to sampling had lower 25-hydroxyvitamin D levels (p = 0.02). Day length was independently associated with 25-hydroxyvitamin D levels (p = 0.02). There was no difference in 25-hydroxyvitamin D levels between baseline and exacerbation; medians 36.2 nmol/L (IQR 22.4-59.4) and 33.3 nmol/L (23.0-49.7); p = 0.43. HRV positive exacerbations were not associated with lower 25-hydroxyvitamin D levels at exacerbation than exacerbations that did not test positive for HRV; medians 30.0 nmol/L (20.4 - 57.8) and 30.6 nmol/L (19.4 - 48.7). There was no relationship between exacerbation frequency and any VDR polymorphisms (all p > 0.05). CONCLUSIONS: Low 25-hydroxyvitamin D levels in COPD are not associated with frequent exacerbations and do not increase susceptibility to HRV exacerbations. Independent of day length, patients who spend less time outdoors have lower 25-hydroxyvitamin D concentration.

Corrigendum to: A rare cause of culture negative bioprosthetic valve endocarditis: a case report of Aggregatibacter aphrophilus infection.

[This corrects the article DOI: 10.1093/ehjcr/ytab003.].

A rare cause of culture negative bioprosthetic valve endocarditis: a case report of Aggregatibacter aphrophilus infection.

Background: The prevalence of culture negative infective endocarditis (IEC) is reported as 2-7% though this figure may be as high as 70% in developing countries.1 This higher rate will, at least in part, be due to reduced diagnostic facilities though some data suggests higher rates even when appropriate cultures were taken. The frequency is significantly elevated in patients who have already been exposed to antibiotics prior to blood cultures.1 , 2 A rare cause of culture negative IEC is the HACEK group of organisms that are normal habitants of the oropharyngeal flora and account for 1-3% of native valve endocarditis.3 Aggregatibacter aphrophilus (A. aphrophilus) is a member of the HACEK group of organisms. Case summary: A 32-year-old gentleman with a previous bioprosthetic aortic valve presented with a 1-week history of diarrhoea, vomiting, malaise, and weight loss. He was awaiting redo surgery for stenosis of the bioprosthesis, which had been inserted aged 17 for aortic stenosis secondary to a bicuspid valve. The initial blood tests revealed liver and renal impairment with anaemia. A transoesophageal echocardiogram demonstrated a complex cavitating aortic root abscess, complicated by perforation into the right ventricle. He underwent emergency redo surgery requiring debridement of the aortic abscess, insertion of a mechanical aortic prosthesis (St Jude Medical, USA), annular reconstruction and graft replacement of the ascending aorta. Despite antibiotic therapy, he remained septic with negative blood and tissue cultures. Bacterial 16S rRNA gene sequencing confirmed A. aphrophilus infection, for which intravenous ceftriaxone was initiated. This was subsequently changed to ciprofloxacin due to neutropenia. The patient self-discharged from the hospital during the third week of antibiotic therapy. One week later, he was re-admitted with fever, night sweats, and dyspnoea. Transthoracic echocardiogram revealed a large recurrent aortic abscess cavity around the aortic annulus fistulating into the right heart chambers; this was confirmed by a computed tomography scan. There was dehiscence of the patch repair. Emergency redo aortic root replacement (25 mm mechanical valve conduit, ATS Medical, USA) and annular reconstruction was performed with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. VA-ECMO was weaned after 3 days. The patient completed a full course of intravenous meropenem and ciprofloxacin and made a good recovery. Discussion: IEC with oropharyngeal HACEK organisms is rare and difficult to diagnose, due to negative blood culture results. The broad-range polymerase chain reaction and gene sequencing with comparison to the DNA database is useful in these circumstances. This case demonstrates the importance of the 16S rRNA gene sequencing for HACEK infection diagnosis and appropriate antibiotic treatment.

Thyroid dysfunction in a UK hepatitis C population treated with interferon-alpha and ribavirin combination therapy.

OBJECTIVE: To assess the incidence of thyroid dysfunction (TD) in a UK cohort of patients with hepatitis C virus (HCV) infection treated with interferon-alpha (IFNalpha) and ribavirin combination therapy (IFN/RBV). DESIGN, PATIENTS AND MEASUREMENTS: A retrospective study of 288 patients who received IFN/RBV for HCV during a 2-year period from January 2006 was performed. Thyroid function was assessed during a 24-week or 48-week course of IFN/RBV. If serum thyrotrophin (TSH) became undetectable (<0.01 mU/l) and serum free thyroxine (T4) was raised, a diagnostic thyroid isotope scan was performed. RESULTS: Full medical records were examined for 260 patients (172 men, 88 women) included in the study, of whom 22.3% (16.9% of men, 33.0% of women) developed TD during IFN/RBV. In total, 10.4% developed a suppressed serum TSH (0.8% Graves' disease, 9.6% transient thyroiditis) while 11.9% developed an elevated serum TSH with 1.5% becoming permanently hypothyroid and requiring levothyroxine therapy. Women had a relative risk (RR) for developing TD of 1.96 (CI: 1.75-3.03, P = 0.004). A serum TSH > or =1.75 mU/l and a positive thyroid peroxidase (TPO) antibody titre pretherapy were associated with RRs for progression to TD of 6.02 (CI: 2.95-12.78, P < 0.0001) and 4.35 (CI: 2.58-6.52; P < 0.0001), respectively, while combination of baseline TSH and TPO antibody data predicted progression to TD with a sensitivity of 94.7%. CONCLUSIONS: Although TD was common in this cohort, just 2.3% developed TD that required ongoing therapy. Pre-IFN/RBV serum TSH and TPO antibody titre were found to predict progression to TD in this group of patients.

Complex presentation of adult-onset Still's disease.

A 61-year-old woman was admitted with feeling generally unwell with influenza-like symptoms, for almost a month. This was followed by dyspnoea, productive cough and fever of >40°C. She was started on oral antibiotics in community, but due to rising inflammatory markers, she was referred for admission to our hospital. Chest X-ray showed left basal pneumonia and SE was started on intravenous antibiotics according to microbiologist's advice. During admission she developed deranged liver functions with right upper quadrant tenderness, pleural and pericardial effusions. This was followed by multiple joint aches, mouth ulcers and a rash on her chest. Finally, after several days and clinical dilemma, she was diagnosed with adult-onset Still's disease by the rheumatologist and was started on prednisolone, to which she showed marked improvement, and was later maintained on methotrexate and hydrotherapy. She was in remission during her follow-up in the rheumatology clinic.

Unexpected early complication of implantable-cardioverter defibrillator.

A 41-year-old woman was visiting Oxford, where she had a sudden cardiac arrest. Cardiopulmonary resuscitation was started by a bystander until the paramedics arrived, who found her in ventricular fibrillation, and delivered three shocks. After 28 min she had return of spontaneous circulation. Emergency coronary angiography revealed normal coronary arteries. Echocardiography followed by a cardiac MRI showed non-dilated left ventricles with no evidence of late gadolinium enhancement. She had a single-chamber implantable-cardioverter defibrillator (ICD). A chest CT showed sternal fracture and subsegmental pulmonary embolism, for which she was anticoagulated and was discharged.Several days later, the patient presented to another hospital with atypical chest pain and dizziness. She had haemodynamic instability and echocardiography showed the ICD lead perforating through the right ventricle, with a large pericardial effusion and tamponade, for which pericardiocentesis was done. Afterwards, the patient had repositioning of the ICD lead safely.

A Physiologically-Based Pharmacokinetic Modeling Approach Using Biomonitoring Data in Order to Assess the Contribution of Drinking Water for the Achievement of an Optimal Fluoride Dose for Dental Health in Children.

Due to an optimal fluoride concentration in drinking water advised for caries prevention purposes, the population is now exposed to multiple sources of fluoride. The availability of population biomonitoring data currently allow us to evaluate the magnitude of this exposure. The objective of this work was, therefore, to use such data in order to estimate whether community water fluoridation still represents a significant contribution toward achieving a suggested daily optimal fluoride (external) intake of 0.05 mg/kg/day. Therefore, a physiologically-based pharmacokinetic model for fluoride published in the literature was used and adapted in Excel for a typical 4-year-old and 8-year-old child. Biomonitoring data from the Canadian Health Measures Survey among people living in provinces with very different drinking water fluoridation coverage (Quebec, 2.5%; Ontario, 70% of the population) were analyzed using this adapted model. Absorbed doses for the 4-year-old and 8-year-old children were, respectively, 0.03 mg/kg/day and 0.02 mg/kg/day in Quebec and of 0.06 mg/kg/day and 0.05 mg/kg/day in Ontario. These results show that community water fluoridation contributes to increased fluoride intake among children, which leads to reaching, and in some cases even exceeding, the suggested optimal absorbed dose of 0.04 mg/kg/day, which corresponds to the suggested optimal fluoride intake mentioned above. In conclusion, this study constitutes an incentive to further explore the multiple sources of fluoride intake and suggests that a new balance between them including drinking water should be examined in accordance with the age-related physiological differences that influence fluoride metabolism.

Comparison of Free Light Chain Assays: Freelite and N Latex in Diagnosis, Monitoring, and Predicting Survival in Light Chain Amyloidosis.

OBJECTIVES: Measurement of serum free light chains (FLCs) is critical in diagnosis, prognosis, and monitoring treatment responses in light chain (AL) amyloidosis. We compare the Freelite assay (polyclonal antibodies to hidden light chain epitopes), which is the current gold standard, with a new assay: a mixture of monoclonal antibodies to light chain epitopes (N Latex). METHODS: We collected 240 serum samples from 94 consecutive patients with newly diagnosed AL amyloidosis (at least three serial serum samples during the first 6 months) analyzed at the National Amyloidosis Centre, London, from January 2011 to April 2012. Concordance in detecting abnormal light chain components and hematologic response was assessed at 2, 4, and 6 months. RESULTS: The κ and λ clonal light chain involvement was 21% and 79%, respectively, with an abnormal κ/λ ratio or detectable protein in 78.7%. Median κ, λ, and difference in involved and uninvolved FLCs by Freelite and N Latex assays were 17.3 vs 16 mg/L (R(2 ) = 0.91), 48.8 vs 52.6 mg/L (R(2) = 0.52), and 43.2 vs 39.1 mg/L, respectively. Discordant κ/λ ratios at presentation were as follows: 10 of 90 abnormal by Freelite/normal by N Latex and 11 of 90 abnormal by N Latex/normal by Freelite. CONCLUSIONS: Both FLC assays show good correlation in detecting the abnormal light chain subtype with discordance in absolute values and thus are not interchangeable.

Coronary artery aneurysm presenting as a large mass encroaching on the right atrium in an adult patient with untreated Kawasaki disease.

A 26-year-old man presented with atypical chest pain and dyspnoea for several days before admission that was not related to exertion. The patient had no medical history other than a long duration of fever and rash as a child, which resolved after a few weeks. The initial blood investigations showed thrombocytopenia and raised inflammatory markers with a negative troponin level. The patient had positive antiplatelet antibodies and was diagnosed with immune thrombocytopenic purpura (ITP). Echocardiography showed a large cystic mass at the right atrium. Coronary multislice CT showed a huge aneurysm at the origin of the right coronary artery (RCA), which was confirmed by coronary angiography. The patient received intravenous immunoglobulin and platelet transfusion before coronary artery bypass surgery and he had a successful resection of the aneurysm with a saphenous vein graft to distal RCA. The patient had a good recovery and was discharged home.

Quetiapine-induced myocarditis presenting as acute STEMI.

An 18-year-old man diagnosed with attention-deficit hyperactivity disorder was recently started on quetiapine in addition to regular methylphenidate, which he had been taking for a number of years. He presented with chest pain and inferolateral ST elevation, and underwent urgent coronary angiography, which showed normal coronary arteries. The initial troponin level was raised and an inpatient echocardiogram showed mild left ventricular systolic dysfunction with no evidence of regional wall motion abnormality. Cardiac MRI showed subepicardial late gadolinium enhancement, which was suggestive of myocarditis. Quetiapine and methylphenidate were discontinued and the patient was discharged home after 1 week. He was followed up within 8 weeks with complete recovery and no symptoms.

Prognosis of Troponin-Positive Patients with Non-Obstructive Coronary Artery Disease.

INTRODUCTION: Troponin elevation is an independent risk factor for mortality, but the prognosis of patients with troponin elevation and non-obstructive coronary artery disease (CAD) is unknown. Recent data have suggested an increased risk of mortality. This study was performed to further investigate the outcomes of troponin-positive patients with obstructive and non-obstructive CAD. METHODS: A retrospective cohort analysis was performed of all patients with raised troponin presenting to Kettering General Hospital (January 2010 to December 2011, n = 1,351). The patients who had angiograms were stratified anatomically into obstructive CAD and non-obstructive CAD (≤50% stenosis). The obstructive CAD group (O-CAD) was sub-analyzed by management strategy: emergency re-vascularization (<12 h), urgent, delayed, and medically managed. Patients with non-obstructive CAD were grouped by the cause of the raised troponin if this could be identified (NO-CAD-I) or cause remained unidentified (NO-CAD-U). The major adverse cardiac and cerebrovascular event (MACCE) and mortality rates were calculated at 30 days and 1-year follow-up. RESULTS: There was a preponderance of hypertension and severe renal impairment in the non-obstructive CAD group. The patients with NO-CAD-U were a low-risk group (MACCE at 1-year follow-up = 0). The remaining NO-CAD-I group had a similar risk to the O-CAD group for MACCE and mortality at 30 days and 1-year follow-up. In fact, at 1-year follow-up, the NO-CAD-I patients when compared with the subgroups of O-CAD, had higher MACCE rates and mortality compared with the emergency re-vascularized group [MACCE: relative risk (RR) (95% CI) = 2.27 (1.29-3.40), P = 0.0047; mortality: RR (95% CI) = 2.08 (1.10-3.93), P = 0.024]. This was driven by higher risk non-cardiac death [RR (95% CI) = 4.10 (1.53-10.99), P = 0.005]. CONCLUSION: Patients with identified cause for raised troponin and non-obstructive CAD are at equivalent risk of MACCE and mortality at 30 days and 1-year follow-up compared to those with obstructive CAD.